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The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis

This study has been terminated.
(Novartis ended all studies regarding Aliskiren.)
Sponsor:
Collaborators:
Novartis
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01067326
First received: February 8, 2010
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

We will study the hypothesis that long-term Tekturna treatment will improve endothelial function and the production and function of endothelial progenitor cells (EPCs) in patients with early atherosclerosis. Specifically, long-term Tekturna treatment will increase the Reactive Hyperemia Peripheral Arterial Tonometry indexes and increase the numbers and the function of circulating endothelial progenitor cells, compared to placebo, in association with a reduction in inflammation and oxidative stress.


Condition Intervention Phase
Endothelial Dysfunction
Drug: Aliskiren
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Tekturna on Endothelial Function and Endothelial Progenitor Cells in Patients With Early Atherosclerosis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Endothelial Progenitor Cells (EPC) [ Time Frame: Baseline, 4 Months ] [ Designated as safety issue: No ]
    Peripheral blood mononuclear cells were stained for EPC markers (cell-surface antigens CD34/CD133/KDR) and counted by flow-cytometry.

  • Reactive Hyperemia Index (RHI) [ Time Frame: Baseline, 4 Months ] [ Designated as safety issue: No ]
    RHI was measured by the noninvasive endothelial peripheral arterial tomography (EndoPat) test. EndoPAT results are reported as the "Endoscore" (range 0-3); a score of 1.67 and lower indicates the need for immediate medical attention; a score between 1.68 and 2 indicates a need to reduce risk factors; a score above 2.1 indicates a healthy heart.


Secondary Outcome Measures:
  • Systolic Blood Pressure [ Time Frame: Baseline, 4 Months ] [ Designated as safety issue: No ]
  • Diastolic Blood Pressure [ Time Frame: Baseline, 4 Months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: February 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aliskiren
150 mg Aliskiren once daily for a period of 4 months.
Drug: Aliskiren
150 mg Aliskiren once daily for a period of 4 months
Other Names:
  • Tekturna
  • Rasilez
Placebo Comparator: Placebo
1 pill per day by mouth for 4 months.
Drug: Placebo
1 pill per day by mouth for 4 months

Detailed Description:

Aliskiren is a direct renin-inhibitor and may have beneficial effects on the vascular endothelium, similar to other antihypertensive therapies targeting the renin-angiotensin-aldosterone system (RAAS). The current study was designed to test the hypothesis that aliskiren improves endothelial function and increases the number of endothelial progenitor cells (EPCs) in normotensive patients with early atherosclerosis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 years old
  2. More than two of the following cardiovascular risk factors (determined by prescreen phone call): family history of cardiovascular disease, physical inactivity/sedentary lifestyle, obesity or overweight, family history of diabetes mellitus or hypertension, total cholesterol > 200 mg/dL, LDL > 130 mg/dL, HDL < 50 mg/dL, smoking, stress, or Triglycerides > 150 mg/dL
  3. Demonstrated endothelial dysfunction (reactive hyperemia - EndoPAT score < 2.0) at time of screening

Exclusion Criteria:

  1. Serum potassium > 5.0 mmol/L documented at any time prior to the study
  2. History of any cardiovascular event (stroke, transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, coronary artery bypass grafting (CABG), percutaneous coronary intervention, hospitalization due to heart failure) during the 3 months prior to the study
  3. Hypertension or hypotension (at Randomization): any patient with Mean Seated Systolic Blood Pressure (msSBP) ≥ 170 mmHg, msSBP < 100 mmHg or Mean Seated Diastolic Blood Pressure (msDBP) ≥ 110 mmHg
  4. Congestive heart failure New York Heart Association (NYHA) class III and IV
  5. Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system blocking agents, e.g. Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II receptor blockers (ARB) or aldosterone-antagonist
  6. Unstable serum creatinine
  7. Second (II) or third (III) degree heart block without a pacemaker
  8. Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia
  9. Clinically significant valvular heart disease
  10. Known renal artery stenosis
  11. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following:

    • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
    • Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
    • Evidence of hepatic disease as determined by a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt
  12. History of malignancy other than basal cell skin cancer within the past five years
  13. Any concurrent life threatening condition with a life expectancy less than 2 years
  14. History or evidence of drug or alcohol abuse within the last 12 months
  15. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
  16. History of hypersensitivity to any of the study drugs or to medications belonging to the same therapeutic class as the study drugs as well as known or suspected contraindications to the study drugs
  17. History of noncompliance to medical regimens or unwillingness to comply with the study protocol
  18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
  19. Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety
  20. Persons directly involved in the execution of this protocol
  21. Pregnant or nursing (lactating) women
  22. Women of Child-Bearing Potential (WOCBP) unless postmenopausal for at least one year, surgically sterile or using effective methods of contraception as defined by local Health Authorities
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01067326

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Novartis
Investigators
Principal Investigator: Amir Lerman, MD Mayo Clinic
  More Information

No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amir Lerman, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01067326     History of Changes
Other Study ID Numbers: 09-007617, R01AG031750, R01HL092954
Study First Received: February 8, 2010
Results First Received: January 9, 2013
Last Updated: January 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Endothelial Dysfunction
Endothelial Function
Tekturna
Endothelial Peripheral Arterial Tomography (EndoPAT)
Progenitor Cells
renin inhibition
endothelial progenitor cells
early atherosclerosis

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Arterial Occlusive Diseases
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014